Vitamin D Receptor Is Required for Proliferation, Migration, and Differentiation of Epidermal Stem Cells and Progeny during Cutaneous Wound Repair.

Vitamin D Receptor Is Required for Proliferation, Migration, and Differentiation of Epidermal Stem Cells and Progeny during Cutaneous Wound Repair.
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皮肤伤口修复过程中表皮干细胞及其后代的增殖、迁移和分化需要维生素 D 受体。

DOI:
10.1016/j.jid.2018.04.033
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发表时间:
2018-11
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
Bikle DD
Bikle DD
中科院分区:
其他
文献类型:
--
作者:
Oda Y;Hu L;Nguyen T;Fong C;Zhang J;Guo P;Bikle DD

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表皮干细胞在表皮再生中起重要作用。当皮肤受伤时,干细胞首先被激活以增殖,随后后代迁移并分化以再生表皮。在这里,我们证明了维生素D受体(VDR)对这些过程的发生至关重要。在条件性VDR敲除小鼠中揭示了VDR对表皮干细胞功能的需求,其中VDR从干细胞和后代中删除,并且小鼠维持低钙饮食。首先,表皮干细胞的自我更新和生态位形成受损。创伤诱导的表皮干细胞活化与β-连环蛋白信号传导的减少相关。第二,创伤诱导的干细胞和后代迁移受损,如VDR沉默细胞的谱系追踪和延迟迁移所示。后代的表皮分化受损与减少E-钙粘蛋白表达相关的伤口部位。VDR的缺失也改变了干细胞的命运,使毛发发育变钝,增加皮脂腺,并改变表皮标志物的表达和位置。这些结果表明,VDR是皮肤伤口愈合过程中表皮干细胞及其后代自我更新、迁移和分化所必需的。
Epidermal stem cells residing in the skin play an essential role in epidermal regeneration. When skin is injured, the stem cells are first activated to proliferate, and subsequently the progeny migrate and differentiate to regenerate the epidermis. Here, we demonstrate that the vitamin D receptor (VDR) is essential for these processes to occur. The requirement for VDR on epidermal stem cell function was revealed in conditional VDR knockout mice, in which VDR was deleted from stem cells and progeny, and mice were maintained on a low calcium diet. First, self-renewal and niche formation of epidermal stem cells were impaired. Wound-induced activation of epidermal stem cells was blunted associated with a reduction of β-catenin signaling. Second, wound induced migration of stem cells and progeny was impaired as shown by lineage tracing and delayed migration of VDR silenced cells. Epidermal differentiation of progeny was impaired at the wounding site associated with reduced E-cadherin expression. Deletion of VDR also changed stem cell fate blunting hair development, increasing sebaceous glands, and altering expression and location of epidermal markers. These results suggest that VDR is required for self-renewal, migration, and differentiation of epidermal stem cells and progeny during cutaneous wound healing.
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